CAMBRIDGE, MA – A device designed to provide a more biologically realistic growth environment for human kidney cells in the laboratory may give scientists a better model to study the effects of disease or new therapeutics on the kidney.
The microscale tissue modeling device, developed by scientists from Draper Laboratory and Boston University, is the first platform to take into account both physical and fluid-flow effects on kidney cells and is a step toward one day replicating kidney organ function in the lab. Their work was published in 2012 in the journal Integrative Biology.
The kidneys are a pair of fist-sized organs that filter blood and are crucial to maintaining fluid balance, regulating blood pressure, and eliminating toxins. Disorders of the kidney can lead to high blood pressure and heart failure, and diabetics are particularly at risk - the World Heath Organization estimates that 10-20% of diabetes-related deaths are due to kidney failure.
The primary structural unit of the kidney, called a nephron, is a highly organized tubule under constant exposure to fluid-flow stress from the blood and fluids it filters. In addition, nephron cells receive cues from the extracellular matrix, a network of structural and signalling proteins. In the laboratory, kidney cells are typically grown on flat plastic or glass surfaces in a static nutrient broth, an unrealistic growth environment which can potentially affect cell function and physiology.
To create a more accurate environment, Else Frohlich, Draper Fellow and Boston University graduate student, and her advisors fabricated a plastic and silicone rubber microdevice comprised of a textured growth surface and a microfluidic chamber. The growth surface, lined with a series of submicron ridges and grooves coated with collagen, mimics topographical and protein cues from the extracellular matrix. On this surface, they grew a layer of cells from a segment of the nephron known as the renal proximal tubule, and provided fluid-flow stress cues with a microfluidic pump.
They found that the combination of topography and fluid-flow enhanced tissue structure formation, and in particular increased the intensity of tight junction formation between the cells, which better resembles kidney cells in the body. These tight junctions act as a seal for filtration and on flat control surfaces, were less well formed.
Frohlich received the President’s Award, the top prize at Boston University’s Science and Engineering Research Symposium, for her work on the project, which contributed to her master’s thesis.
“We’re pushing the cells toward more realistic behavior,” says Joseph Charest, director of the organ-assist and in vitro models programs at Draper. “You can then model how well they replace and transport fluids, look at disease progression, and test potential therapies.”
The team is currently improving the device design and is testing permeability of the kidney cells to compare with how they function in the body. They plan on screening drugs and adding more cell types from other segments of the nephron in the future. “Eventually it would be great to create a full nephron-on-a-chip,” says Frohlich.